Treatment of lupus nephritis: facing the era of immunotherapy

Lupus nephritis (LN) is a major cause of morbidity and mortality, affecting over half of SLE patients. The traditional treatment protocol with cyclophosphamide and corticosteroids dramatically improved patient and renal survival, but conferred a heavy burden of side effects. In addition, not all patients respond to first-line immunosuppression; 35% suffer at least one episode of renal relapse and 5-20% develop end-stage renal disease. Over the last decade, the increasing understanding of the complex pathogenesis underlying lupus nephritis and accelerating advances in molecular and cellular immunology have paved the way for development of immunomodulatory therapies for LN. In contrast to the global immunosuppressive effects of conventional treatment, these biologic agents target specific pathways that contribute to the inflammatory response, aiming to reduce tissue damage while preserving immunocompetence. The goal of this review is to highlight some of the more promising novel immunomodulators, including Abetimus sodium, Rituximab, Epratuzumab, Abatacept, Belimumab, Tocilizumab and Infliximab, and discuss how these agents affect central pathways in the pathogenesis of disease.